Biology subjects

Berns, M.

Publications and source records attributed to Berns, M..

2 recordsLinked to original sources

bioRxiv2018

Biphasic recruitment of TRF2 to DNA damage sites promotes non-sister chromatid homologous recombination repair

TRF2 binds to telomeric repeats and is critical for telomere integrity. Evidence suggests that it also localizes to non-telomeric DNA damage sites. However, this recruitment appears to be precarious and functionally controversial. We find that TRF2 recruitment to damage sites occurs by a two-step mechanism: the initial rapid recruitment (phase I) and stable and prolonged association with damage sites (phase II). Phase I is poly(ADP-ribose) polymerase (PARP)-dependent and requires the N-terminal basic domain. The phase II recruitment requires the C-terminal MYB/SANT domain and the iDDR region in the hinge domain, which is mediated by the MRE11 complex and is stimulated by hTERT. PARP-dependent recruitment of intrinsically disordered proteins contributes to transient displacement of TRF2 that separates two phases. TRF2 binds to the I-PpoI-induced DNA double-strand break sites, which is enhanced by the presence of complex damage and is dependent on PARP and the MRE11 complex. TRF2 depletion affects non-sister chromatid homologous recombination (HR) repair, but not HR between sister chromatids or non-homologous endjoining pathways. Our results demonstrate a unique recruitment mechanism and function of TRF2 at non-telomeric DNA damage sites.\n\nSummary StatementTRF2 is recruited to DNA double-strand break damage sites by a two-step mechanism and functions in non-sister chromatid homologous recombination repair

cell biology↗

bioRxiv2017

Positive Feedback Between Contractile Ring Myosin and Ring-Directed Cortical Flow Drives Cytokinesis

During cytokinesis, an equatorial actomyosin contractile ring constricts at a relatively constant overall rate despite its progressively decreasing size. Thus, the per-unit-length rate of ring closure increases as ring perimeter decreases. To understand this acceleration, we monitored cortical surface and ring component dynamics during the first division of the C. elegans embryo. We show that the polar cortex expands during ring constriction to provide the cortical surface area required for division. Polar expansion also allows ring myosin to compress cortical surface along the pole-to-pole axis, leading to a continuous flow of cortical surface into the ring. We propose that feedback between ring myosin and compression-driven cortical flow drives an exponential increase in the amount of ring myosin that maintains the high overall closure rate as ring perimeter decreases. We further show that an analytical mathematical formulation of the proposed feedback, called the Compression Feedback model, recapitulates the experimental observations.\n\nIMPACT STATEMENTDuring cytokinesis, positive feedback between myosin motors in the contractile ring and compression-driven cortical flow along the axis perpendicular to the ring drives constriction rate acceleration to ensure timely cell separation.\n\nMAJOR SUBJECT AREASCell biology, Computational and Systems Biology

cell biology↗